Flexible Bronchoscopy 4th Edition

Ko-Pen Wang
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Flexible Bronchoscopy
Flexible Bronchoscopy

Fourth Edition

Edited by
Ko-Pen Wang, MD
Division of Pulmonary and Critical Care Medicine
Johns Hopkins Bayview Medical Center
Johns Hopkins University School of Medicine
Baltimore, MD, USA

Atul C. Mehta, MD, FACP, FCCP

Lerner College of Medicine
Buoncore Family Endowed Chair in Lung Transplantation
Department of Pulmonary Medicine
Respiratory Institute
Cleveland Clinic
Cleveland, OH, USA

J. Francis Turner, Jr., MD, FACP, FCCP, FCCM

Division of Pulmonary and Critical Care Medicine
University of Tennessee Graduate School of Medicine
Knoxville, TN, USA;
National Supercomputing Institute
University of Nevada, NV, USA
This edition first published 2020 © 2020 by John Wiley & Sons Ltd.
Edition History [3e, 2012]

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Library of Congress Cataloging‐in‐Publication Data

Names: Wang, Ko Pen, editor. | Mehta, Atul C., editor. | Turner, J.
Francis, Jr., editor.
Title: Flexible bronchoscopy / edited by Ko-Pen Wang, Atul C. Mehta,
J. Francis Turner, Jr.
Description: Fourth edition. | Hoboken, NJ : John Wiley & Sons, 2020. |
Includes bibliographical references and index.
Identifiers: LCCN 2019058267 (print) | LCCN 2019058268 (ebook) | ISBN
9781119389057 (hardback) | ISBN 9781119389224 (adobe pdf) | ISBN
9781119389217 (epub)
Subjects: MESH: Bronchoscopy | Bronchial Diseases–diagnosis | Bronchial
Diseases–therapy
Classification: LCC RC734.B7 (print) | LCC RC734.B7 (ebook) | NLM WF 500
| DDC 616.2/307545–dc23
LC record available at https://lccn.loc.gov/2019058267
LC ebook record available at https://lccn.loc.gov/2019058268
Cover Design: Wiley
Cover Images: Courtesy of Professors Kurimoto and Miyazawa, Courtesy of J. Francis Turner, Courtesy of Yang Xia, Courtesy of Eric Carlson
and Tom Schlieve, © yodiyim/Getty Images

Set in 9.5/12.5pt STIXTwoText by SPi Global, Pondicherry, India

10 9 8 7 6 5 4 3 2 1
 v

Contents

List of Contributors ix
Preface xiii
About the Companion Website xv

1 A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 1

Heinrich D. Becker

2 Professor Ikeda’s Genius: The Flexible Bronchoscope and Flexible Bronchoscopy Training 21
Jason Akulian and David Feller-Kopman

3 Applied Anatomy of the Airways 27

Mani S. Kavuru, Atul C. Mehta, and J. Francis Turner, Jr.

4 Infection Control and Radiation Safety in the Bronchoscopy Suite 35

Prasoon Jain, Sarah Hadique, and Atul C. Mehta

5 Anesthetic Management for Diagnostic and Therapeutic Bronchoscopy 63

Blake A. Moore, J. Francis Turner, Jr., and Ko-Pen Wang

6 Indications and Contraindications in Flexible Bronchoscopy 81

Robert F. Browning Jr., J. Francis Turner, Jr., and Ko-Pen Wang

7 Radial-Probe Ultrasonography in Flexible Bronchoscopy 103

Noriaki Kurimoto, Takeshi Isobe, Takeo Inoue, and Teruomi Miyazawa

8 Convex-Probe Ultrasonography in Flexible Bronchoscopy 111

Andrew Pattison and Kazuhiro Yasufuku

9 Early Diagnosis of Lung Cancer: Autofluorescence Bronchoscopy, Narrow-Band Imaging, Optical Coherence
Tomography, Raman Spectroscopy 127
Renelle Myers and Stephen C.T. Lam

10 Electromagnetic Navigation Bronchoscopy 137

Carlos Aravena Leon and Thomas R. Gildea

11 Virtual Bronchoscopic Navigation 155

Swati Baveja, Wolfgang Hohenforst-Schmidt, J. Francis Turner, Jr., and Ko-Pen Wang

12 Indirect Laryngoscopy: Anatomy and Use of the Flexible Bronchoscope 161

Eric R. Carlson and Thomas Schlieve
vi Contents

13 Bronchoscopy for Airway Lesions: Washing, Brushing, and Endobronchial Biopsy 179
Heinrich D. Becker

14 Bronchoalveolar Lavage 185

Wei Zhang, Yi Huang, and Richard Helmers

15 Bronchoscopic Lung Biopsy 207

Sean McKay, Robert F. Browning Jr., J. Francis Turner, Jr., and Ko-Pen Wang

16 Transbronchial Needle Aspiration for Cytology and Histology Specimens 221

Yang Xia, J. Francis Turner, Jr., Atul C. Mehta, and Ko-Pen Wang

17 Staging of Bronchogenic Carcinoma: Our Path from 1994 to the Present 251
J. Francis Turner, Jr. and Ko-Pen Wang

18 The Future of Interventional Pulmonology 263

Ala Eddin Sagar and David E. Ost

19 Application of Laser, Electrocautery, Argon Plasma Coagulation, and Cryotherapy

in Flexible Bronchoscopy 271
Danai Khemasuwan and Semra Bilaceroglu

20 Flexible Bronchoscopy and the Application of Endobronchial Brachytherapy, Fiducial Placement,

Radiofrequency Ablation, and Microwave Ablation 285
Michael A. Jantz

21 Foreign Body Aspiration and Flexible Bronchoscopy 319

Erik E. Folch, Alexander S. Rabin, and Atul C. Mehta

22 The Role of Bronchoscopy in Hemoptysis 333

Guo-wu Zhou, Hai-dong Huang, Chong Bai, and Sunit R. Patel

23 Endobronchial Stents 351

Septimiu D. Murgu, Jonathan S. Kurman, J. Francis Turner, Jr., Atul C. Mehta, and Ko-Pen Wang

24 Balloon Bronchoplasty 379

Ben Bevill, Luca Paoletti, and Nicholas J. Pastis Jr.

25 Rigid Bronchoscopy 387

J. Francis Turner, Jr. and Ko-Pen Wang

26 Pediatric Flexible Bronchoscopy 397

Xicheng Liu, Chen Meng, Jing Ma, and Shunying Zhao

27 Bronchoscopy in the Intensive Care Unit 411

Ali Sadoughi and Alexander Chen

28 Bronchial Thermoplasty Management of Asthma 421

Ara A. Chrissian, Samir Makani, and Michael J. Simoff
 Contents vii

29 Endoscopic Management of Emphysema 433

Stefano Gasparini and Martina Bonifazi

30 Endoscopic Management of Bronchopleural Fistulas 445

Ming-yao Ke, Hai-dong Huang, and J. Francis Turner, Jr.

31 Clinical Management of Benign Airway Stenosis and Tracheobronchomalacia 455

Qiang Li and Yang Xia

Index 471
 ix

List of Contributors

Jason Akulian, MD, MPH Eric R. Carlson, DMD, MD, FACS

Section of Interventional Pulmonology Department of Oral and Maxillofacial Surgery
Division of Pulmonary and Critical Care Medicine University of Tennessee Medical Center University of
University of North Carolina at Chapel Hill Tennessee Cancer Institute
Chapel Hill, NC, USA Knoxville, TN, USA

Chong Bai, MD, PhD

Alexander Chen, MD
Respiratory and Critical Care Medicine
Division of Pulmonary and Critical Care
Changhai Hospital
Washington University School of Medicine
Second Military Hospital
St Louis, MO, USA
Shanghai, China

Swati Baveja, MBBS Ara A. Chrissian, MD

Division of Pulmonary and Critical Care Medicine Pulmonary and Critical Care
University of Tennessee Graduate School of Medicine Loma Linda University
Knoxville, TN, USA Loma Linda, CA, USA

Heinrich D. Becker, MD
David Feller-Kopman, MD
Formerly Department of Interdisiplinary Endoscopy
Interventional Pulmonology
Thoraxclinic at Heidelberg University
Division of Pulmonary and Critical Care Medicine
Heidelberg, Germany
Johns Hopkins University School of Medicine
Ben Bevill, MD Baltimore, MD, USA
Division of Pulmonary and Critical Care Medicine
University of Tennessee Graduate School of Medicine Erik E. Folch, MD, MSc
Knoxville, TN, USA Division of Pulmonary and Critical Care Medicine
Massachusetts General Hospital
Semra Bilaceroglu, MD
Boston, MA, USA
Izmir Dr Suat Seren Training and Research Hospital for
Thoracic Medicine and Surgery
Health Sciences University Stefano Gasparini, MD, FCCP
Izmir, Turkey Department of Biomedical Sciences and Public Health
Universita Politecnica delle Marche
Martina Bonifazi, MD Ancona; and
Department of Biomedical Sciences and Public Health Pulmonary Diseases Unit
Università Politecnica delle Marche, Ancona; Department of Internal Medicine
Pulmonary Diseases Unit Azienda Ospedaliero‐Universitaria ‘spedali Riuniti’
Department of Internal Medicine Ancona, Italy
Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’
Ancona, Italy
Thomas R. Gildea, MD, MS, FCCP
Robert F. Browning Jr., MD, FACP, FCCP Department of Pulmonary
Interventional Pulmonology Allergy and Critical Care Medicine
Walter Reed National Military Medical Center, Bethesda; Respiratory Institute
Uniformed Services University of Health Sciences Cleveland Clinic
Bethesda, MD, USA Cleveland, OH, USA
x List of Contributors

Sarah Hadique, MD Mani S. Kavuru, MD

Department of Pulmonary and Critical Care Medicine Division of Pulmonary and Critical Care Medicine
West Virginia University Jefferson Center for Critical Care
Morgantown, WV, USA Thomas Jefferson University and Hospital
Philadelphia, PA, USA
Richard Helmers, MD
Mayo Clinic Health System Ming-yao Ke, MD
Eau Claire, WI, USA Department of the Respiratory Centre
Second Affiliated Hospital of XiaMen Medical College
Wolfgang Hohenforst-Schmidt, MD Xiamen, Fujian, China
Sana Clinic Group Franken
Department of Cardiology/Pulmonology/Intensive Care/ Danai Khemasuwan, MD, MBA
Nephrology Tufts University School of Medicine and
“Hof” Clinics St Elizabeth’s Medical Center
University of Erlangen Boston, MA, USA
Hof, Germany
Noriaki Kurimoto, MD
Hai-dong Huang, MD
Division of Medical Oncology and Respiratory Medicine
Respiratory and Critical Care Medicine
Department of Internal Medicine
Second Military Medical University
Shimane University Hospital
Shanghai;
Izumo, Japan
Interventional Pulmonology Center of SMMU
Respiratory and Critical Care Medicine
Changhai Hospital Jonathan S. Kurman, MD
Second Military Medical University (SMMU) Division of Pulmonary and Critical Care
Shanghai; Department of Medicine
International Training Center for Interventional Medical College of Wisconsin
Pulmonology Milwaukee, WI, USA
Henry Ford Hospital
Shanghai, China Stephen C.T. Lam, MD, FCCP
Department of Integrative Oncology
Yi Huang, MD British Columbia Cancer Agency
Shanghai Changhai Hospital Vancouver, British Columbia;
Shanghai, China Cancer Imaging Department and
Department of Medicine
Takeo Inoue, MD
University of British Columbia
Division of Respiratory Medicine
Vancouver, British Columbia, Canada
Department of Internal Medicine
St Marianna University School of Medicine
Carlos Aravena Leon, MD
Kawasaki, Japan
Department of Pulmonary
Takeshi Isobe, MD Allergy and Critical Care Medicine
Division of Medical Oncology and Respiratory Medicine Respiratory Institute
Department of Internal Medicine Cleveland Clinic
Shimane University Hospital Cleveland, OH, USA;
Izumo, Japan Department of Respiratory Diseases
Faculty of Medicine
Prasoon Jain, MD, FCCP Pontificia Universidad Catolica de Chile
Louis A. Johnson VA Medical Center Santiago, Chile
Clarksburg, WV, USA
Qiang Li, MD
Michael A. Jantz, MD Department of Respiratory and Critical Care Medicine
Division of Pulmonary, Critical Care, and Sleep Medicine Shanghai East Hospital
University of Florida Tongji University School of Medicine
Gainesville, FL, USA Shanghai, China
 List of Contributors xi

Xicheng Liu, MD Renelle Myers, MD, FRCPC

Department of Interventional Pulmonology Department of Integrative Oncology
Beijing Children’s Hospital British Columbia Cancer Agency
Capital University of Medicine Vancouver, British Columbia;
Beijing, China Department of Medicine
University of British Columbia
Jing Ma, MD Vancouver, British Columbia, Canada
Department of Interventional Pulmonology
Qilu Children’s Hospital of Shandong University David E. Ost, MD, MPH, FACP
Jinan, China Division of Internal Medicine
Department of Pulmonary Medicine
Samir Makani, MD MD Anderson Cancer Center
Division of Pulmonary and Critical Care Medicine University of Texas
Henry Ford Hospital Houston, TX, USA
Detroit, MI, USA
Luca Paoletti, MD
Sean McKay, MD Division of Pulmonary and Critical Care Medicine
Interventional Pulmonology Medical University of South Carolina
Walter Reed National Military Medical Center Charleston, SC, USA
Uniformed Services University of Health Sciences
Bethesda, MD, USA
Nicholas J. Pastis Jr., MD, FCCP
Division of Pulmonary and Critical Care Medicine
Atul C. Mehta, MD, FACP, FCCP
Medical University of South Carolina
Professor of Medicine
Charleston, SC, USA
Lerner College of Medicine
Buoncore Family Endowed Chair in Lung Transplantation
Department of Pulmonary Medicine Sunit R. Patel, MD
Respiratory Institute Medical Group
Cleveland Clinic Trulock, CA, USA
Cleveland, OH, USA
Andrew Pattison, MD
Chen Meng, MD Division of Thoracic Surgery
Department of Interventional Pulmonology Toronto General Hospital
Qilu Children’s Hospital of Shandong University University Health Network
Jinan, China University of Toronto
Toronto, Ontario, Canada
Teruomi Miyazawa, MD, PhD, FCCP
Division of Respiratory Medicine Alexander S. Rabin, MD
Department of Internal Medicine Department of Pulmonary and Critical Care Medicine
St Marianna University School of Medicine Massachusetts General Hospital
Kawasaki, Japan Boston, MA, USA

Blake A. Moore, MD
Ali Sadoughi, MD
Section on Cardiothoracic Anesthesia
Division of Pulmonary and Critical Care
University of Tennessee Graduate School of Medicine
Albert Einstein College of Medicine/Montefiore Medical
Knoxville, TN, USA
Center
Septimiu D. Murgu, MD New York, USA
Department of Medicine
Section of Pulmonary and Critical Care Ala Eddin Sagar, MD
University of Chicago Banner MD Anderson Cancer Center
Chicago, IL, USA Phoenix, AZ, USA
xii List of Contributors

Thomas Schlieve, DDS, MD Yang Xia, MD

Division of Oral and Maxillofacial Surgery Division of Pulmonary and Critical Care Medicine
University of Texas Southwestern Medical School Second Affiliated Hospital of Zhejiang University School
Parkland Memorial Hospital of Medicine
Dallas, TX, USA Hangzhou, China

Michael J. Simoff, MD, FCCP Kazuhiro Yasufuku, MD, PhD

Division of Pulmonary and Critical Care Medicine Division of Thoracic Surgery
Henry Ford Hospital Toronto General Hospital
Detroit, MI, USA University Health Network
University of Toronto
J. Francis Turner, Jr., MD, FACP, FCCP, FCCM Toronto, Ontario, Canada
Division of Pulmonary and Critical Care Medicine
University of Tennessee Graduate School of Medicine Shunying Zhao, MD
Knoxville, TN; Department of Interventional Pulmonology
National Supercomputing Institute Beijing Children’s Hospital
University of Nevada Capital University of Medicine
Las Vegas, NV, USA Beijing, China

Ko-Pen Wang, MD Guo-wu Zhou, MD, PhD

Division of Pulmonary and Critical Care Medicine Respiratory and Critical Care Medicine
Johns Hopkins Bayview Medical Center Changhai Hospital
Johns Hopkins University School of Medicine Second Military Hospital
Baltimore, MD, USA Shanghai;
Respiratory and Critical Care Medicine
Wei Zhang, MD China-Japan Friendship Hospital
Shanghai Changhai Hospital Beijing, China
Shanghai, China

Preface
We are honored to be the editors of the fourth edition of
Flexible Bronchoscopy. In this role, we wish to recognize
that this book is the collaborative efforts of many experts in
the art and science of bronchoscopy, as reflected by the
contributions of our eminent authors.
The art of bronchoscopy is now recognized as a critical
skill not only in the technical performance of obtaining
necessary tissue and a variety of therapeutics, but also to
ensuring the best application of our rapidly expanding
technology.
Modern bronchoscopy was born over 100 years ago when
Professor Gustav Killian began utilizing the rigid broncho-
scope in 1897. This was followed by the genius of Professor
Shigeto Ikeda in developing the flexible bronchoscope in
1964. Since these early years, technology has enhanced our
capabilities at a steady pace with intermittent brilliant
leaps forward with the insight of modern thought leaders
and inventors since the 1970s. These developments are
well known to the field of bronchoscopy and interventional
pulmonology. They include the development of the flexible
transbronchial needle for nodal aspiration and broncho-
scopic lung cancer staging, followed by Professors Heinrich
Becker, Teruomi Miyazawa, Kazuhiro Yasufuku, and oth-
ers shepherding the application of ultrasound in the tra-
cheobronchial tree. Also, we acknowledge the seminal
work of Professor François Dumon and the development
of silicone stents in 1990, and other advances as detailed by
the authors in this textbook.
xiii
In this book, our authors delineate the bedrock tech-
niques of bronchoscopy, such as anesthesia for bronchos-
copy, rigid bronchoscopy, and bronchoscopic lung biopsy.
Also covered are the history and applications of the more
recent developments of linear and radial‐probe ultrasound,
navigational bronchoscopy for localization and sampling
of peripheral pulmonary nodules, as well as authoritative
information on therapeutic procedures such as ablative
therapy utilizing “hot” instruments with laser, electrocau-
tery, and argon plasma coagulation or “cold” interventions
utilizing spray cryotherapy.
As bronchoscopy and interventional pulmonology
mature as a specialty, the challenge will be to explore how
we might best apply this burgeoning technology in an
effective, safe, and economically prudent manner. Optimal
application of many standard techniques still yields sub-
stantial benefit in the diagnosis and staging of benign and
malignant disease while new techniques need to be care-
fully judged against the established ones.
This is an exciting time for those of us privileged to be
helping patients with diseases of the chest through our
interest in the art and science of bronchoscopy. We hope
that the wisdom and enthusiasm shared by our authors
will allow you to excel in your chosen profession and
improve the welfare of our patients.
Ko‐Pen Wang
Atul C. Mehta
J. Francis Turner, Jr.
 xv

About the Companion Website

Don’t forget to visit the companion website for this book:

www.wiley.com/go/wang4e

There you will find valuable video material designed to enhance your learning.
Scan this QR code to visit the companion website.

A Short History of Flexible Bronchoscopy
From Fiberoptics to Robotics
Heinrich D. Becker
Department of Interdisiplinary Endoscopy, Thoraxclinic at Heidelberg University, Heidelberg, Germany
It is already 70 years since the beginning of broncho-
scopic examination and the appearance of the flexible
bronchofiberscope represents the opening of a new
page in bronchoscopic examination. Future broncho-
scopic examinations should make further progress on
this milestone of the flexible bronchofiberscope.
(Shigeto Ikeda [1])
1.1 ­Introduction
There is ample literature about the history of bronchos-
copy in general. In this chapter, I will describe the steps
that led to the development of the first flexible broncho-
scope from prototype to the final device and the crucial
steps of further evolution from fiberscopes to video-
scopes, endobronchial ultrasound (EBUS) scopes, and
the latest robotic flexible bronchoscope. The introduc-
tion of adjuvant technologies created a wide range of
diagnostic and therapeutic applications for flexible bron-
choscopy that has made it the central indispensible tool
in pulmonary medicine today. I will describe how, driven
by changing concepts, planned search for technical solu-
tions or chance detection, new technologies were added
to existing ones, leading to new concepts and strategies
in a logical pattern. The examples given are early and
advanced lung cancer, central airway obstruction, soli-
tary pulmonary nodules (SPN), diseases of lung tissue,
emphysema, and asthma. And finally, based on current
developments I will take a look at the future of flexible
bronchoscopy.
Flexible Bronchoscopy, Fourth Edition. Edited by Ko-Pen Wang, Atul C. Mehta, and J. Francis Turner, Jr.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/wang4e
1
1.2 ­Shigeto Ikeda
and the Invention of the Flexible
Bronchoscope
From its introduction by Gustav Killian in 1897, the rigid
bronchoscope remained the standard instrument for
inspection of the airways during the following 70 years.
Due to the comparatively complicated procedure, requir-
ing special skills and in many cases additional general
anesthesia, application of rigid bronchsocopy was mainly
restricted to ENT departments, thoracic surgery, and
­specialized pulmonology centers. Only after Shigeto Ikeda
introduced the flexible bronchoscope in 1967 did the
art of bronchoscopy spread to many medical disciplines
worldwide.
Ikeda was born in 1925 (Figure 1.1). After graduating
from high school, he began studying medicine at Keio
University in 1944. However, he had to interrupt his stud-
ies for one year as he suffered from specific pleuritis and
underwent thoracoplasty. After recovery, he graduated in
1952 but in the same year, he had to have lung resection for
a tuberculous mass during his internship in the Division of
Tuberculous Surgery. Here he began studies on bronchial
anatomy, including bronchography and motion pictures.
As he found illumination by electric bulbs at the tip of rigid
telescopes unsatisfactory, in 1962 he designed a telescope
with “cold light.” A glass fiber bundle, connected to a 500 W
xenon light source, was attached to the telescope and pro-
vided sufficient illumination for obtaining photographs
and taking movies, for which he constructed special
cameras.
2 Flexible Bronchoscopy

However, visualization of the bronchi in both upper

lobes was often difficult due to the anatomical structures.
Thus the need for a flexible bronchoscope, based on the
concept of the gastrointestinal fiberscope presented by
Basil Hirshowitz in 1961, was apparent [2,3]. As Machida
Co. and Olympus Optical Co. had produced the first gastro-
fiberscopes in Japan from 1962, Ikeda approached Machida
in 1964 and Olympus in 1965 for the construction of proto-
types for bronchoscopy. He formulated specific require-
ments regarding diameter, more and smaller optical fibers,
flexible light guide, fixed tip <1 cm, length 1 m, fixed focus
0.5–3 cm, visual angle 80°, and tip flexion of 60°. For ease
of introduction, a special semiflexible orotracheal tube was
constructed, that could be straightened in case specimens
had to be obtained by a rigid forceps (Figure 1.2).
In 1966, when Ikeda presented the first prototype at the
9th International Congress on Diseases of the Chest in
Copenhagen, Denmark, he created huge excitement and
the story was even published in the New York Times. Further
improvements were made on the following prototypes: con-
trol mechanisms for lengthwise rotation and bending of the
tip were built into the control section, improved imaging
was achieved by regular arrangement of smaller glass fib-
ers, and a lens was mounted on the tip (Figure 1.3, movie).
Finally, in the seventh prototype a channel was integrated
Figure 1.1 Shigeto Ikeda, 1925–2001. into the scope for the introduction of sampling devices;
Ikeda was confident that the instrument was ready for

Figure 1.2 Ikeda demonstrating the first bronchoscope at my first visit to Japan. (Note: he was left handed, which is why the line to
the light source and the suction of flexible bronchoscopes are running to the left so that the control section of the scope rests easily
in your left hand and the lines are not pulling.) On the left is the first scope with the special orotracheal tube that could be
straightened for taking rigid biopsies.

Figure 1.3 Movie clip of the first flexible fiberscope (see video
on the website: function with flexion and rotation).
Source: Courtesy of T. Shirakawa.
commercialization and introduced and popularized flexible
fiberbronchoscopy throughout the world.
In the following years, more and more experience was
gained in clinical application and by 1980 flexible fiber
bronchoscopy had become a routine procedure and spread
worldwide. In 1980, after visiting Dumon in Marseille,
Ikeda’s group began Nd:YAG laser treatment and photody-
namic therapy (PDT) of malignant lesions. For better
image resolution and processing, together with Asahi
Pentax Co. he introduced charge-coupled device (CCD)
chip technology to build the first videoscope which was
Figure 1.4 With Teruomi Miyazawa at Ikeda’s tomb. The inscription on the gravestone beneath the emblem of the WAB reads:
“Invention.”
A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 3
later adopted by Machida-Toshiba and Olympus. On his
mission to promote the art of flexible fiberbronchoscopy,
Ikeda traveled extensively all over the world and in 1978
founded the World Association for Bronchology (WAB)
within which nowadays, as the World Association for
Bronchology and Interventional Pulmonology (WABIP),
national and continental assocations are united.
In recognition of his outstanding achievements, Ikeda
received many national and international awards. After
resignation from his clinical and academic positions in
1991, he preserved a keen interest in the development of
bronchoscopy and stayed closely connected to the scientifc
societies. Despite his fragile health due to several strokes
and heart attacks, according to his lifelong motto “Never
give up,” he attended all the meetings until the year 2000
before he died in 2001 [1,4–8] (Figure 1.4).
1.3 ­Further Development
of Flexible Endoscopes
In the beginning, Machida and Olympus were the only
manufacturers of flexible fiberbronchoscopes but soon
other companies in Japan, the US and Europe began enter-
ing the market and today there are around 20 in business.
As Olympus had the widest distribution network, it
remains the main player in the market. With growing
experience in fiberbrochoscopy, there was an increasing
demand for different types of bronchoscopes for special
4 Flexible Bronchoscopy
(a)
(c)
Figure 1.5 Modern flexible scopes of different diameters and sizes of biopsy channels.
diagnostic and therapeutic applications and also for other
disciplines in medicine that realized the value of the new
technology, such as anesthesia, pediatrics, and ICU
medicine.
The development of new imaging and therapeutic tech-
nologies that could be applied via flexible bronchoscopes
drove new advances. Improved fiberbronchoscopes were
brought to the market in comparatively quick succession.
Different diameters from 6 mm down to 2.2 mm for periph-
eral airways and pediatric use became available (Figure 1.5).
Recently, miniaturized bronchoscopes with an outer diam-
eter of less than 1 mm have been constructed for laboratory
research in small animals. A variety of bronchoscopes with
wide channels of 3 mm for interventional procedures and
1.2 mm for peripheral use are now available. Improvement
of fiberoptics is allowing better analysis of small structures
and photodocumentation. For observation by trainees, a
teaching attachment (lecture scope) can be mounted onto
the control section of the bronchoscope. Fiberscopes with
battery illumination and integrated monitor are useful for
(b)
the ICU, sleep laboratory, on wards and in the outpatient
department.
The next big step was the introduction of videobron-
choscopy by Pentax in 1987, which became possible due to
miniaturization of CCD chips, that could be integrated into
the tip of flexible bronchoscopes instead of optical fibers
[9] (Figure 1.6). Via a video processor, moving images can
be followed on a monitor, stored on film and data banks,
and printed. They can be directly integrated into the report
or transmitted online to other departments. The biggest
advantage is that images can be processed according to
colors, contour enhancement, magnification, and different
light sources. The CCDs have become so efficient that
today videbronchoscopes with high-definition television
(HDTV) with superior image quality are available. In very
small endoscopes, the CCD is integrated into the control
section and transmits the fiberoptic image to the processor
(hybrid scope).
The next technological revolution was the introduction
of EBUS in 1996, adding a new dimension to flexible

Figure 1.6 The exponential downsizing of
CCD chips for endoscopes.
Figure 1.7 Radial miniature EBUS probe inserted via the channel of a flexible bronchoscope and ultrasonic bronchoscope, so-called
convex probe (cP) bronchoscope.
bronchoscopy by widening the view of the bronchoscopist
beyond the airway. In 1999, the miniaturized radial probe
was launched, that could be introduced via the biopsy
channel of the flexible bronchoscope [10]. As there was an
increasing demand for real-time transbronchial needle
aspiration of mediastinal lymph nodes (TBNA), a dedi-
cated ultrasonic endoscope was added in 2002 [11]
(Figure 1.7) Today, EBUS-TBNA has become the standard
for mediastinal staging and the radial probe for approach to
peripheral lesions. “Endobronchial ultrasound (EBUS) is
the single most useful pulmonary procedure in decades
and should be available to all patients with thoracic ade-
nopathy requiring evaluation” (Kevin L. Kovitz).
The latest revolution in flexible bronchoscopy is the
introduction of robotic bronchoscopy. In the attempt to
A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 5
become more independent from the bronchoscopist’s indi-
vidual skills in handling and accuracy, robotic surgery has
been developed. It is expected to improve access to periph-
eral airways by flexibility in all directions in order to place
tools with precision consistently in the desired location
and maintain stability in position under vision and by
active remote robotic control. In 2018, a paper on clinical
application of the first robotic bronchoscope (Monarch®,
Auris Surgical Robotics Inc.) was published by my former
coworker Jose Rojas-Solano [12] (Figure 1.8) A second
upcoming robotic platform is the Ion™ endoluminal sys-
tem by Intuitive Surgical, Inc., which currently is waiting
for 510(k) clearance.
A general problem with flexible bronchoscopes is
­disinfection because of the small channels with risk of
6 Flexible Bronchoscopy
cross-contamination [13]. As few optical systems can with-
stand the autoclaving procedure, disposable videobron-
choscopes have been developed [14]. The costs of reusable
bronchosopes have been assessed for application in the
ICU which, albeit with many imponderables, seemed
favorable. However, due to the many different diagnostic
and therapeutic applications of flexible bronchoscopy as
illustrated below, it is highly improbable that disposable
flexible bronchoscopes will be taking over more than the
current approximately 30% of the market. So far, the only
practical solution is high-level disinfection of instruments
and strict observation of hygienic guidelines.
With all these technical improvements, bronchoscopy
has become an essential part of pulmonary medicine. The
bronchoscope market is driven by increasing prevalence of
pulmonary diseases that can be diagnosed and treated by
minimal invasive procedures with the bronchoscope,
improved reimbursement, and technological advance-
ments. The global market was valued at US$15.4 billion in
2017 and is expected to have increased 8.3% annually by
the year 2025. Thus it can be expected that this will be an
important incentive for manufacturers to research and
invest in innovations [15].
1.4 ­Further Developments
in Flexible Bronchoscopy
The ease of application and access beyond the central air-
ways opened vast opportunities for the introduction of
new optical, diagnostic, and therapeutic techniques [16],
starting with transbronchial lung biopsy (TBLB),
Figure 1.8 J. Rojas-Solano with the Monarch
robotic bronchoscope.
­ erformed by Anderson and Zavala after Ikeda’s visit to
p
the United States [17].
In 1974, Reynolds published first experiences with bron-
choalveolar lavage (BAL) [18]. Cortese demonstrated the
potential of early lung cancer detection by fluorescence,
induced by injection of hematoporphyrin derivates (HPD)
in 1978 [19]. In the same year, Wang began TBNA of medi-
astinal lymph nodes via the flexible bronchoscope, which
by then was only rarely applied via rigid instruments [20].
Also, the first endobronchial application of the Nd:YAG
laser was performed by Toty [21] and in 1980 Dumon pub-
lished his results on photoablation of stenoses by ND:YAG
laser treatment, which for some time was the most applied
technique [22,23]. In parallel, Hayata and Kato applied
PDT after sensitization by HPD for treatment of centrally
located early lung cancer [24]. In 1979 Hilarss used radio-
active probes for treatment of central airway cancer for
endoscopic high-dose radiation therapy (HDR) [25].
With rapid development and miniaturization of elec-
tronic imaging by charge CCDs, the first videobroncho-
scope was developed by Ikeda in cooperation with Pentax
Co. in 1987. In 1990, the first dedicated silicone stent for the
airways was presented by Dumon [26]. As implanting sili-
cone stents by flexible bronchoscopy is difficult and intra-
vascular metallic stents proved unsuitable for the airways,
we introduced the Ultraflex® Nitinol® stent in 1992 [27]. In
1991 Lam reported on autofluorescence bronchoscopy
(AFB) without HPD for early detection of lung cancer [28].
The need for local staging of these lesions was met by the
introduction of radial EBUS in 1999 [10], which in addition
opened a wide range of applications for diagnosis within
the mediastinum and lung. Currently, in connection with

(a)
(c)
Figure 1.9 Live transmission of an EBUS procedure from Heidelberg, Germany, to Yokohama, Japan, at the WCB. Endoscopy setting (a),
communication center in the endoscopy unit (b), hardware (“brain”) in the endoscopy for communication (c), live presentation on the
screen in the lecture hall (d).
TBNA by a dedicated ultrasonic bronchoscope, it is widely
replacing mediastinoscopy for staging of lung cancer [29].
Early detection of lung cancer created further demand for
new imaging modalities by high-power magnification vid-
eobronchoscopes and narrow band imaging (NBI) for
­analysis of subtle vascular structures [30]. Endoscopic opti-
cal coherence tomography (EOCT) providing information
on the layer structure of the bronchial wall with higher
resolution than EBUS is currently under investigation for
bronchology [31].
Maneuvering smart diagnostic tools inside the airways
beyond the visible range has been enhanced by smart elec-
tromagnetic navigation (EMN) [32,33], which also sup-
ported bronchoscopic treatment of peripheral lesions by
insertion of brachytherapy catheters [34]. The first results
of studies for treatment of asthma by thermic destruction
of the bronchial muscles [35] and of emphysema by inser-
tion of endobronchial valves have been published [36].
A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 7
(b)
(d)
The rapid growth of internet communication opened
new avenues for communication to enhance consulting,
research, and teaching. The first long-distance live trans-
mission on the occasion of the 12th World Congress for
Bronchology and Bronchoesophagology was performed
between Heidelberg, Germany, and Yokohama, Japan, in
2000 (Figure 1.9). Further details of all these innovations
are beyond the scope of this article and interested readers
will find suggestions for reading in the references.
1.5 ­Current Concepts
and Strategies in Flexible
Bronchoscopy
During my professional life, around 600 physicians from all
over the world came to our institution to obtain experience
in all kinds of procedures. Frequently, younger doctors
8 Flexible Bronchoscopy
were surprised to observe that, apart from obtaining skills
in a special technique, they learned that bronchoscopy is
part of the wider concept of pulmonary medicine. This is
why it might be useful to illustrate the evolution of flexible
bronchoscopy in more detail by some current issues in
interventional bronchoscopy.
1.6 ­Detection and Staging of Early
Lung Cancer in the Central Airways
While applying PDT treatment of advanced lung cancer, it
was observed that invisible small lesions in the bronchial
mucosa became visible due to HPD fluorescence. This
proved useful for detection of so-called early lung cancer,
that is, in patients with positive sputum cytology with radi-
ologically invisible lesions that could potentially be cured.
In further studies, it was shown that by illumination with
special light sources, the bronchial mucosa fluoresced
without activation by HPD and several systems have been
developed in fiberscopes and videoscopes for detection of
early cancers by autofluorescence.
As autofluorescence was unspecific for diagnosis of
malignancy, methods for further analysis were added.
Magnifying videobronchoscopes allow more detailed
analysis of intra- and subepithelial structure, especially
pathological vessels, that are characteristic of development
of early bronchial cancer. By selecting smaller spectra in
RGB imaging, narrow band imaging (NBI), the visuali-
zation of characteristic pathological vessels could be mark-
edly improved. Further increase of resolution toward
almost microscopy level could be achieved by EOCT in
which an optical scanning beam is reflected from the dif-
ferent layers of the mucosa, providing optical histology
images. The most recent technology, confocal microen-
doscopy, is finally bringing optical resolution to the
­cellular level [37].
It is expected that combination of these methods might
finally replace histological examination on biopsy speci-
mens. When early lesions were treated by very efficient
local therapy, such as PDT, there were always a considera-
ble number of patients who had only partial remission of
their tumors. By definition, in situ carcinoma does not
transgress the lamina propria of the mucosa and early lung
cancer does not invade the cartilage and the connective tis-
sue layer in between. The latter in particular could not be
assessed by optical methods.
In the 1990s, together with Olympus, we developed a
dedicated radial ultrasound (EBUS) probe of 20 MHz.
The high resolution of its images clearly showed all the
layers of the bronchial wall. When we analyzed “early
cancers” detected by autofluorescence, frequently the
lesions extended further into the bronchial wall, even into
the adjacent tissue and small lymph nodes that evaded
diagnosis by computed tomography (CT) [38]. When by
EBUS exploration only strictly localized tumors were
treated by PDT, in all patients long-lasting complete
remission was achieved [39]. Thus it was proven that it
was not failure of the PDT, as had been assumed, but of
local staging of these lesions. Which means that suppos-
edly early lesions should be explored by the described
methods, before a decision on the method of endoscopic
treatment is made. Thus in a more extensive localized
lesion, if surgery is not considered, endobronchial brachy-
therapy might be preferable because of its deeper penetra-
tion (Figure 1.10).
1.7 ­Diagnosing and Staging
of Advanced Lung Cancer
Correct staging of lung cancer is the prerequisite for
­successful treatment [40]. The introduction of flexible
­bronchoscopy allowed visualization of segmental and sub-
segmental airways and in this way significantly helped to
assess the endoluminal extension of cancers, which is espe-
cially important for delineation of the prospective resection
lines for thoracic surgery (Figure 1.11). Also, preoperative
bronchoscopy is essential to exclude additional endobron-
chial metastasis. As the vision of the bronchoscope is lim-
ited to the lumen and the internal surface of the bronchial
wall, involvement of the deeper layers or penetration into
the mediastinal structures could be only indirectly assessed.
Because radiological exploration of the mediastinum
depends on the contrast between water density, air, fat, or
calcium, we experienced a lot of misdiagnosis because no
such interface was present. Especially when in solid tumors
adjacent to the mediastinum, infiltration of those structures
was diagnosed by radiology, this could often not be con-
firmed during surgery. Also diagnosis of lymph node metas-
tasis based on size was of only limited value.
This is why in 1989 I approached Olympus who were
already active in gastrointestinal ultrasonography, to develop
EBUS for exploration, especially with regard to staging of
lymph nodes. During the following 10 years, many obstacles
had to be overcome because of the special conditions in
the airways. However, after many protototypes, two EBUS
­systems had been developed, the radial probe and the ultra-
sonic endoscope, that are now widely used in different
indications. By using EBUS, tumor compression of the air-
ways versus infiltration of the wall can be reliably differenti-
ated in the preoperative bronchoscopic evaluation [41].
Most important for bronchoscopic staging is involvement
of mediastinal lymph nodes. With the rigid bronchoscope
(a) (b)

(c) (d)

Figure 1.10 Early lung cancer. The slight discoloration on white light becomes very prominent by autofluorescence (a). By magnifying
endoscopy, the pathological vascularization becomes visible (b), which is even more prominent under NBI (c). In the EBUS image, the
superficial lesion ventrally is thickened (3 mm) compared to the normal wall on the left (1.4 mm), but well within the confines of the
bronchiall wall and can be treated by bronchoscopic intervention (d).

(a) (b) (c) (d)

Ir 192

Tumor at bifurcation Laserresection before HDR HDR Scar at 2y

(e) (f) (g)

Uberlebenswahrscheinlichkeit

1.0

0.8
Relative

0.6
Komplette
0.4 Remission

0.2
Partielle Remission

0 1 2 3 4
Jahre

Survival after HDR Stenosis after 4 y After dilation and stenting

Figure 1.11 Extensive squamous cell cancer at the bifurcation extending into the trachea (a). Immediately after Nd:YAG laser
resection (b). Isodose lines around the Ir 192 radioactive probe (c). Bifurcation two years after HDR therapy (d). Survival of patients
with complete remission compared to partial remission after HDR (e). Recurrent high-grade radiogenic stenoses after complete
remission (f). Recanalization after balloon dilation by insertion of three Nitinol stents (g).
10 Flexible Bronchoscopy
TBNA of mediastinal masses and enlarged lymph nodes
had been performed but was never widely used. This
changed with the introduction of the flexible bronchofiber-
scope. After localizing enlarged lymph nodes in relation to
bronchial landmarks on CT, guided TBNA, such as the
main carina and bronchial branchings, special flexible
cytology or histology needles can be easily passed through
the airway wall, even in a bent position, inaccessible for
rigid needles. The method was very safe, complications
mainly anecdotal and the results were so good that in many
cases TBNA replaced mediastinoscopy, back then the gold
standard for staging. But despite that, TBNA remained
widely underused, mainly probably for fear of bleeding
from larger mediastinal vessels.
With the introduction of the radial ultrasound probe,
lymph node localization, especially in the paratracheal region
where there are no clear landmarks, became more reliable. In
the paratracheal region, results of EBUS-guided TBNA were
significantly superior. However, only after the introduction
of the dedicated ultrasound bronchoscope, by which real-
time observation of the needle passing into the lesion is pos-
sible, did EBUS-guided TBNA become widely accepted and
today it is the recommended standard for mediastinal staging
and has widely replaced mediastinoscopy [42].
1.8 ­Tumors of the Central Airways:
From Palliation to Cure
With the increasing incidence of lung tumors, one main
indication for bronchoscopy had become central airway
obstruction. In contrast to rigid bronchoscopy, mechanical
ablation by the flexible instrument itself, apart from
necrotic fragile tissue, is mostly not successful. Resection
by forceps, curette, or other mechanic instruments is tedi-
ous due to their small size. One exception in special cases is
balloon dilation of malignant airway stenosis by com-
pression [43]. The effect, however, is short-lived and not
very efficient for improvement of dyspnea.
For rapid desobliteration, several methods have been
introduced. In 1982, Dumon described the application of
the Nd:YAG laser for thermal destruction of cancer tissue
for rapid relief of central airway obstruction. After attend-
ing Dumon’s lecture in 1980, Ikeda visited him in Marseille
and immediately introduced the laser in Japan. The advan-
tage was the noncontact destruction by vaporization of the
tissue. By observation of risk factors, application of short
impulses at maximum 40 W power setting and 50% oxygen
supply, the method was very safe. In 1997, Homasson
described high-frequency (HF) electrocautery that uses
the thermal effect of electric current for the destruction of
tissue and by its immediate effect is comparable to the
Nd:YAG laser. Sutedja called it “the poor man’s laser” as it
has a similar effect at much lower costs [44 45]. A variation
of electrodestruction is argon plasma coagulation (APC)
[46]. In this noncontact method, the current is induced by
heating argon gas to separate the electrons from the atoms
and the resulting Ar + plasma is the medium for transfer of
the electric current. In contrast to methods that destroy tis-
sue by heat, cryotherapy uses the Joule–Thomson effect
of creating cold by rapid expansion of liquefied gases in
small catheters. This can be used for removal of the adher-
ing frozen tissue by rapid extraction of the probe or for
inducing delayed tumor necrosis due to intracellular ice
crystal formation [47].
All the above methods provide immediate relief of symp-
toms and in malignancies have to be repeated after recur-
rence, unless definitive treatment for cure can be provided.
Survival after laser resection of malignancies in my experi-
ence was 20% after three years. For patients who could not
be cured by surgery or radiotherapy after local resection,
endoscopic methods for long-term palliation were sought.
In the early 1990s, local long-term palliation of endobron-
chal cancer with high dose-rate intraluminal irradiation
(HDR brachytherapy) by insertion of catheters armed with
a radioactive Ir192 probe at the tip was investigated. The prin-
ciple is application of a very high dose of radiation near the
radiation source with a steep gradient to spare the surround-
ing tissues. We added HDR to laser treatment. When we were
able to achieve endoscopic complete remission, the long-
term effect lasted many years, in some patients even resulting
in cure. Our strategy is application of 2–3 sessions of external
radiation to reduce the tumor volume and then four sessions
at 5 Gy by endoluminal radiation [48].
In patients with complete remission, long-term complica-
tions frequently included extensive scar formation resulting
in recurrence of severe central airway stenoses. These can
only be treated by internal support. In 1989, Dumon pre-
sented his dedicated silicone stent that could be placed by
rigid bronchoscopy. Anecdotal reports described techniques
for implantation with the fiberscope it but never gained
wider use. Instead, endovascular stent systems were adapted
for insertion into the airways. However, the first expandable
and self-expanding metallic stents made from stainless
steel and tantalum either collapsed due to missing internal
support, as in blood vessels, or perforated due to excessive
pressure on the airway wall. After negative experiences
with tantalum stents, we developed the Boston Scientific
Nitinol stent, later called the Ultraflex stent (Figure 1.12).
After improving the insertion mechanism and development
of an additional covered version, it became the standard
model for flexible insertion. Some of my patients have been
living with this stent for more than 20 years, one after inser-
tion at the age of 2 years.

(a)
Figure 1.12 Dumon silicone stent (a) and covered Ultraflex Nitinol stent (b).
Parallel to laser therapy, PDT for bronchial cancer was
introduced. By this treatment, cancer tissue is sensitized to
light by injection of HPD which, during laser illumination, is
degraded and obliterates capillary vessels and destroys cancer
cells due to oxygen radical production. However, in contrast to
Nd:YAG laser resection, the effect of treatment is delayed and
not recommended for emergency situations. But it is very effi-
cient as an adjunct to acute interventions and can also be
applied in conjunction with brachytherapy or after placement
of uncovered stents in order to treat tumor ingrowth.
A possibly promising recent approach for treatment of
inoperable lung cancer is bronchoscopic intratumoral
injection of anticancer agents such as ethanol, chemo-
therapeutics, or immunostimulatory genes. For better
local control of the injection, EBUS-guided transbronchial
needle injection (EBUS-TBNI) offers visual control by
measuring tumor volume for dose calculation, avoiding
intravascular injection and observing the hypoechoic
swelling by fluid injection [49].
1.9 ­Diagnosis and Treatment
of Peripheral Lung Cancer
Over recent decades, a gradual shift has occurred from
centrally located lung cancer to peripheral lesions in the
lung. As in early endobronchial cancer, the prognosis of
A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 11
(b)
peripheral cancer improves the earlier it is detected. This
is why screening programs for early detection by low-dose
spiral CT have been investigated. After long-term follow-
up, it could be shown that significantly more smaller
lesions were found and that mortality could be reduced by
20% [50]. However, when SPN were routinely resected, it
turned out that half were benign and in fact did not need
surgery with its side-effects [51]. This is why there was a
demand for preoperative confirmation of the histology.
With flexible tools like washing, brushing, curettes, nee-
dles, and biopsy forceps, there exists a wide armamentar-
ium for obtaining histopathological material.
The challenge is finding the path toward the lesion,
because calculating the location of the lesion from X-ray or
CT and trying to approach it merely by endoscopic view
has a very low success rate. Real-time control of transbron-
chial biopsy under fluoroscopy was better [52]. But the
visualization of lesions under 2 cm and ground glass opaci-
ties is very poor. Anecdotal reports of transbronchial biop-
ies under real-time CT visualization were more successful,
but the logistic challenges and radiation exposure pre-
vented widespread application [53]. After introduction of
radial EBUS, it became possible to confirm the exact posi-
tion of the SPN and the path via which it could be
approached. When the probe was introduced via a guide
sheath that could be left in place as an “extended working
channel” for introducing tools, the results became much
12 Flexible Bronchoscopy

(a) (c)

Operator Console
Controller Rack

Robotic Endoscope

Patient Side System

(b)

A
Sheath Biopsy instrument Target lesion

Bronchoscope

Illumination
B C
Robotic Endoscope
Camera
Illumination Fibers

Camera Cleaning (Irrigation/Aspiration)

Bronchoscope Handle

Working Channel Working Channel

Sheath Handle

Figure 1.13 The Monarch robotic endoscope system (RES). The proximal controlling system and the robotic endoscope (a), the
bronchoscope (b) and the endoscopic view of the peripheral tumor and the biopsy procedure (c). For an information video clip see
www.aurishealth.com/monarch-platform

better [54]. However, especially in the upper lobes, the path
toward the lesion is frequently hard to find and, moreover,
the radial probe is not steerable. This is why we investi-
gated a system for EMN, analogous to a GPS, to introduce
a catheter into the lung periphery of the lung.
The patient is placed with the upper body within a low-
intensity electromagnetic field (serving as “satellite”) and a
sensor (board computer in GPS) can be followed on a mon-
itor moving through the overlaid image of the patient’s CT
scan (road map). The important feature is that the sensor is
mounted on the tip of a steerable guide that can be turned
360° while moving it through an extended working chan-
nel to the periphery. After reaching the lesion, the sensor
is removed and with EBUS the intralesional position can
be confirmed. With an ultra-slim bronchoscope, observation
of the intrapulmonary airway is possible to assess whether
forceps biopsy in endoluminal growth or needle biopsy
and transbronchial biopsy in external compression is
­preferable. An alternative technique for navigation is
­introduction of a smaller bronchoscope along a path cre-
ated by virtual bronchocopy and overlaid on the real
endoscopy image [55].
Navigation has significantly improved diagnosis of SPN
and has become the standard for approaching these lesions.
Yet, as in all interventional bronchchoscopic procedures,
success also depends on the individual skills of the bron-
choscopist. Therefore, robotic bronchoscopy was devel-
oped to offer an alternative approach to address the
limitations of current bronchoscopic techniques for biopsy
of peripheral lung lesions. In a paper published recently by
 A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 13

my former coworker Dr. Rojas-Solano, very promising
results with the first commercially available robotic
endoscopy (RES) (Auris Surgical Robotics, San Carlos,
CA) were reported.
RES consists of a 3.2 mm videobronchoscope with a
1.2 mm working channel and an outer sheath, which both
allow four-way steering by two robotic arms under contin-
uous remote, direct, and visual front view control. The
bronchoscope’s distal section can achieve 180° of deflec-
tion in any direction. The proximal section allows for con-
trol of irrigation and aspiration (Figure 1.13).
With reliable tools for the approach to SPN and EBUS
control of stable positioning of the extended working
channel, endoscopic treatment of inoperable peripheral
cancer became feasible. Considering the most similar
endoscopic treatment compared to curative surgery after
our experience with localized central airway cancer, we
decided to apply peripheral brachytherapy as we could
easily match the dosage to the primary tumor and also to
the peribronchial lymphatics and hilar lymph nodes when
moving the source centrally through the airways. Following
our first experience in a small study, we could achieve long-
standing complete remission in the majority of cases [56]
(Figure 1.14). Other modalities in planning or currently
under investigation are radiofrequency ablation (RFA),
laser, cryotherapy, PDT, and vapor ablation.
1.10 ­Parenchymal Lung Disease
Although, with improved CT imaging, many causes of
interstitial lung diseases display pathognomonic morpho-
logical patterns, frequently histomorphological or micro-
biological confirmation for diagnosis is necessary. Right
from the beginning of fiberbronchoscopy, taking samples
by washing and brushing was used for this purpose.
Whereas this proved useful in diagnosing infectious lung
diseases and lung cancer in cases of positive cytology, the
small amounts of fluid did not suffice for diagnosis of
parenchymal lung diseases.

(a) (b) (c) (d)

(e) (f) (g)

(h) (i) (j)

Figure 1.14 Diagnosis and treatment of peripheral lesions. Conventional navigation via three monitors for endoscopy, fluoroscopy,
and EBUS (a). The electromagnetic navigation system (EMN, superDimension) with sensor, electromagnetic board and computer with
control monitor (b). The sensor (green) is maneuvered into the target lesion (yellow) under three-plane CT control on the monitor (c).
The intralesional position is confirmed by introducing the EBUS probe (d). To assess the best biopsy technique, an ultra-thin Olympus
endoscope is introduced and forwarded toward the lesion (e–g). As the lesion protrudes into the lumen, forceps biopsy is the
appropriate technique for obtaining tissue samples (h). In case of inoperability, by the same procedure a brachytherapy catheter can be
inserted (i) and HDR therapy can be applied according to calculation by the isodose lines (j).
14 Flexible Bronchoscopy
However, as sometimes characteristic cells were
observed, in the early 1980s a method with instillation of
larger amounts of fluid for sampling specimens from the
bronchoalveolar space was introduced – bronchoalveolar
lavage (BAL). Initially, it was expected that BAL provided a
nonbloody biopsy method, for example by the relation of
T-helper to T-suppressor cells for sarcoidosis. But in further
studies this hope did not hold true, as the findings were
frequently unspecific. Findings were characteristic only for
limited, comparatively rarer diseases such as eosinophilic
pneumonia or alveolar proteinosis. Only in severe infec-
tions, especially in immunocompromised patients, is it still
widely used. In most cases, examination of lung tissue for
diagnosis is needed.
After Anderson demonstrated the safety of taking trans-
bronchial biopsies by forceps from lung tissue via the flexi-
ble bronchoscope, this method became state of the art in
(a)
(c)
Figure 1.15 Transbronchial cryobiopsy. With EMN, a catheter is inserted into a peripheral lesion (a) and the cryoprobe is inserted (b).
After defreezing the probe is removed together with the catheter and the bronchoscope (c). Comparison of biopsy sizes with cryoprobe
and large biopsy forceps (d).
diagnosis of lung diseases and SPN. As the specimens are
pretty small, the sampling error can be reduced by taking sev-
eral biopsies from different segments of one lung. In our expe-
rience, using a larger forceps that is not pulled out through
the biopsy channel increases positive results. For this pur-
pose, we introduce the flexible scope through an endotracheal
tube, as Ikeda described in his first publication, and leave the
forceps in front of the endoscope tip. This way, we are taking
up to one specimen from each segment in one lung with a
very low rate of complications, which also gives us informa-
tion on disease activity in different parts of the lung [57].
The safety of taking larger specimens encouraged the use
of cryobiopsy probes, by which much larger tissue frag-
ments can be obtained at an equally low complication rate.
In addition, pathologists prefer these samples because they
have much less mechanical damage than in forceps biop-
sies [58] (Figure 1.15).
(b)
(d)

1.11 ­Treatment of Lung Function
Disorders: Emphysema and Asthma
In 1996, a paper by Cooper et al. was published about the
favorable results after bilateral lung volume reduction in
patients with severe emphysema [59]. On the basis of
these results, the National Emphysema Treatment Trial
(NETT) Research Group was founded to perform a pro-
spective randomized trial of lung volume reduction sur-
gery [60]. The primary optimism was later corrected
because a considerable number of patients were at high
risk of death after lung volume reduction surgery [61].
The result after thoracic surgery could not be reversed, so
bronchoscopic reversible solutions for endoscopic lung
volume reduction (ELVR) were investigated. As the
potential market of chronic obstructive pulmonary dis-
ease (COPD) patients was considered huge, several com-
panies began developing different devices, valves, coils,
and vapor ablation to exclude overextended lung tissue
from ventilation.
Valve implantation has been studied in three rand-
omized controlled and several noncontrolled trials, show-
ing a benefit for patients with minimal interlobar or no
collateral ventilation. A reduction of lobar lung volume by
56–80% in association with a significant improvement in
lung function of about 20% in predominant upper lobe
emphysema was observed. The main complication is pneu-
mothorax in up to 23% [62,63]. Coil implantation has been
studied in a single randomized controlled trial, which
showed a significant improvement in quality of life.
Bronchoscopic thermoablation has been shown to reduce
lobar volume by an average of 48% also in patients with
emphysema mainly affecting the upper lobes. Whereas
valves are reversible, coils are not easily removable and
vapor ablation is irreversible. Treatment by ELVR should
currently be restricted to experienced centers [64].
The principle for treatment of severe refractory asthma
by bronchial thermoplasty (BT) is the assumption that
by preventing contraction of the smooth muscles of the air-
ways, severe asthma attacks can be reduced. Via a radiofre-
quency probe, formed like a Dormia basket, controlled heat
is applied to the airway wall, interrupting the smooth mus-
cles without lasting damage to the other structures. After a
feasibility study showed the efficacy and safety and longer
lasting positive effect of the treatment, a long-term multi-
center study was performed. The data showed that BT is
an effective and safe therapy. The improvements in
asthma control based on reduction in severe exacerba-
tions and emergency room visits were maintained for a
long time. A single BT treatment comprising three proce-
dures ­provides long-term benefit for at least five years.
BT has become an important addition to the treatment
A Short History of Flexible Bronchoscopy: From Fiberoptics to Robotics 15
a­ rmamentarium for patients with severe persistent asthma
who remain ­symptomatic despite taking inhaled corticos-
teroids and long-acting beta-agonists [65].
1.12 ­The Future of Flexible
Bronchoscopy
You can’t connect the dots looking forward; you can
only connect them looking backward. So you have
to trust that the dots will somehow connect in your
future. (Steve Jobs, quoted in [66])
1.12.1 Factors for Predicting Future
Developments
Based on my experience and further research, I will sketch
out here what might be the future developments in flexible
bronchoscopy [67–69]. Of course, it is not possible to pre-
dict the future exactly but developments can be predicted
as some are improvements of existing techniques, others
driven by demand for solutions of problems. Some technol-
ogy is developed for other purposes and transferred to
bronchoscopy (like fiberbronchoscopy and EBUS). Some
are completely new techniques (like chips, computers, and
robots). New technology can be disruptive and stop further
progress. And finally, there is serendipity – detection by
pure chance (penicillin, polymerase chain reaction) which
is completely unpredictable. All these factors will increase
as new technology is appearing with exponential speed.
Last but not least, adoption depends on acceptance by
customers, which in my experience is the most unpredict-
able part of any innovator’s dilemma. If they are lucky,
patient, and have enough support, finally they may suc-
ceed in installing a new technology. For radial EBUS, it
took 10 years, from the first contact in 1989 of convincing
the company to invest, to develop the technology and con-
vince physicians of its usefulness, until it entered the mar-
ket. But then convex-probe EBUS became available three
years later, as it was highly demanded, which almost killed
the radial probe before its additional usefulness was recog-
nized. Another, in my opinion beautiful, instrument, vibra-
tion response imaging (VRI), an electronic stethoscope
that made breathing visible, was never understood or
accepted and finally failed to enter the market, despite hav-
ing been approved by the FDA [70,71].
1.12.2 Imaging
The gaps in resolution, field of view, and penetration are
continuously closing. Thus, with high magnification,
EOTC, cellular analysis by microconfocal scanning
16 Flexible Bronchoscopy

­ icroscopy, and in vivo immunostaining optical biopsy will

m even by a joystick on a monitor, as with the robotic bron-
become reality. New in vivo imaging procedures of func-
tional status such as ciliary beat, local bronchial and pul-
monary interstitial inflammation, contraction of the
bronchial muscles, bronchial and mediastinal blood flow,
and tracheobronchial airflow will provide new insights
into pathomechanisms and also generate new technologies
for noninvasive local treatment.
1.12.3 Steering
The robotic bronchoscope is navigated by remote control as
a human–machine interface. New optical and tactile sen-
sors will assist in guiding endoscopes. Force feedback sys-
tems will be integrated into “intelligent” instruments such
as forceps, needles, snares, baskets, and other tools that
will give an artificial impression of the forceps to the opera-
tor who is no longer actually maneuvering these instru-
ments directly by their hands but via telemanipulator or
choscope. Instrument diameters are becoming so small
that steering by conventional tendon wire technology is no
longer applicable. The bending mechanism will be pro-
vided by shape memory alloy (SMA) technology and
micromachines at the tip will be applied. True robots will
no longer need to interface with humans but will indepen-
dently perform diagnostic and therapeutic procedures
based upon computerized feedback data. Humans will
only be on hand to interfere by troubleshooting.
1.12.4 Intervention
Miniaturized instruments such as forceps, needles, and
suturing devices made from SMAs will revolutionize inter-
vention. Needle injection of cytotoxic agents or gene ther-
apy, radio waves, microwaves, and high-intensity focused
ultrasound (HIFU) will be applied with the use of a new
endoscope generation. Biotechnology is applied in seeding

(a) (b)

(c) (d)

Figure 1.16 Visions of future technologies. Head-mounted device with two monitors for 3D imaging (a). Remote navigation under
monitor control by track ball device (b). Navigation by virtual bronchoscopy with electronic glove (c). Long-distance navigation of
imaginary capsular endoscope via joystick (d).

grafts and biodegradable devices are investigated for tem-
porary stenting of the airways. In future, we may replace
damaged structures such as mucosa and cartilage in postin-
tubation stenosis by endoscopic cell seeding on 3D-printed
scaffolds or implantation of cultured bioprostheses, cre-
ated from the patient’s own stem cells.
1.12.5 Communication
System integration will be essential for complete docu-
mentation and communication. The heterogeneous
devices have to be integrated by complex systems for con-
nection, transformation of images to MPEG standards,
for storage on video servers and steering of complex video
networks. Digital systems support documentation and
storage of data. They also support planning of procedures,
rational management of resources and manpower as well
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Professor Ikeda’s Genius
The Flexible Bronchoscope and Flexible Bronchoscopy Training
Jason Akulian1 and David Feller-Kopman 2
1
Section of Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
2
Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2.1 ­Professor Shigeto Ikeda
(1925–2001): The Father of Flexible
Bronchoscopy
Prior to the development of the flexible bronchoscope in
1965, endobronchial evaluation and treatment were per-
formed using direct visualization via rigid bronchoscopy.
The introduction of the rigid bronchoscope by Gustav
Killian in 1876 and its subsequent adoption by otolaryn-
gologists allowed for the visualization of the trachea and
central airways. Application of rigid bronchoscopy evolved
from simple visualization of the airway to include the
retrieval of foreign bodies, diagnosis of aortic aneurysms,
enlarged lymph nodes, removal of diphtheria-related air-
way pseudomembranes, and treatment of airway pathol-
ogy associated with pulmonary tuberculosis [1,2]. These
developments represented major advancements in the
treatment of airway disease but it was acknowledged that
the scope’s rigid design carried with it inherent limitations.
These limitations included an inability to visualize the
upper lobes or subsegments of the middle lobe and bilat-
eral lower lobes [2]. In 1962, the Japanese National Cancer
Center was founded [3]. There, and in the same year, a
team led by Dr Shigeto Ikeda (1925–2001) (Figure 2.1)
developed the glass-fiber light guide for use during
esophagoscopy and rigid bronchoscopy, replacing the use
of distal electric light bulbs and improving distal scope
illumination.
In the five years following development of the glass-fiber
light guide, two important developments occurred that
cemented Dr Ikeda’s reputation as the father of flexible
bronchoscopy. The first was the collection of case data at
the newly founded National Cancer Center in Tokyo.
Dr Ikeda was able to describe the airway distribution of
Flexible Bronchoscopy, Fourth Edition. Edited by Ko-Pen Wang, Atul C. Mehta, and J. Francis Turner, Jr.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/wang4e
21
c­ ancers resected during this period and noted that 48 cases
could be considered “early pulmonary cancers” (resected
specimens less than 3 cm). He went on to report that only
20.8% (10/48) of these cases would have been visible utiliz-
ing a rigid bronchoscope. Dr Ikeda described the need for a
flexible bronchoscope that could not only visualize the
upper lobes but would also be able to reach the distal air-
ways (segments II–IV). This flexible bronchoscope would,
in his opinion, potentially make an additional 62.4%
(30/48) of lesions visible [2]. Dr Ikeda’s recognition of these
issues and his experience working with the Machida
Corporation in development of the glass-fiber light guide
led him to request production of a prototype flexible bron-
choscope in the spring of 1964 [4]. Specifications for the
prototype included but were not limited to an outer diam-
eter less than 6 mm, image and light guide fibers of 15 μm,
and flexion of the distal tip (Table 2.1). One year later, simi-
lar specifications were presented to the Olympus Optical
Company. In the summer of 1966, both Machida and
Olympus submitted their prototype designs which were
subsequently presented at the 9th International Congress
on Diseases of the Chest in Copenhagen, Denmark.
Subsequent iterations of the flexible bronchofiberscope
included but were not limited to the addition of a working
channel, improved durability, and distal tip flexion. The
next major developments in the evolution of the flexible
bronchoscope occurred in 1987 when the Asahi Pentax
Corporation introduced a scope with a distal camera eye
and a miniaturized charge-coupled device sensor placed
into the tip, replacing the need for fiberoptic image bundles
and improving image resolution [5]. The Olympus and
Machida-Toshiba corporations quickly followed suit and
introduced similar models. This “videobronchoscope”
­represented the first generation of what is now considered
22 Flexible Bronchoscopy

Soon after the introduction of the “modern” flexible

­videobronchoscope, it became a ubiquitous and vital tool
in the practice of pulmonology and thoracic surgery. Its
use further expanded to military/law enforcement and
industrial applications including airplane engine and
public water line inspection.
Further evolution of the flexible videobronchoscope
occurred in 2004 with the introduction of the flexible
curvilinear endobronchial ultrasound videobroncho-
scope (EBUS) [6,7]. This advancement coupled the
hybrid fiber videobronchoscope with an ultrasound
head, allowing for real-time evaluation and sampling of
structures outside the airway and otherwise invisible to
direct visualization via white light bronchoscopy. In the
more than 50 years since Dr Ikeda first conceived of the
flexible bronchofiberscope, we have seen amazing
advances on the technology. We can now “see,” biopsy,
and stage the hilum and mediastinum as well as drive to
many more generations than previously thought possible
using ultra-thin bronchoscopes. It has been upon this
original platform of the flexible bronchoscope that fur-
ther technological advances such as electromagnetic
navigation bronchoscopy and now the potential for
robotic bronchoscopy have developed.

2.2 ­Flexible Bronchoscopy Training

and Education
Figure 2.1 Dr Shigeto Ikeda. Source: Reproduced with
With the development of the flexible bronchoscope and its
permission of Wolters Kluwer Health Inc.
subsequent advances, a need for procedure-specific train-
ing and education was recognized. The first attempts at
Table 2.1 Flexible fiberbronchoscope specifications (1964) education centered on textbooks illustrating bronchial
anatomy, disease states and tips on bronchoscope manipu-
Outer diameter (mm) <6 lation [8–10]. In 1975, Zavala published the first large case
series of diagnostic fiberoptic bronchoscopy performed in
Image guide fiber (thickness and 15 μ, >15 000 600 patients between 1971 and 1974 [11]. Dr Zavala
number) described bronchoscope insertion, maneuvering and
Light guide fiber (thickness and 15–20 μ, >10 000 biopsy techniques employed by his team during bronchos-
number)
copy. He also discussed specimen handling and processing
Length of distal rigid part (mm) <10 as well as postprocedural care of the equipment used. In
Focal distance (fixed focus, cm) 0.5–3.0 this work was described the two most common diagnoses
Tip flexion angle 60°, 30 mm from distal established through bronchoscopic biopsy: malignant and
tip infectious. Finally, he attempted to quantify the diagnostic
Field of vision 80° yield of each technique as well as procedural complica-
Overall length (cm) 100 tions. In 1974, prior to Dr Zavala’s publication, the
American College of Chest Physicians (ACCP) appointed a
subcommittee representing thoracic surgeons, otolaryn-
the “modern” flexible bronchoscope and has since under- gologists, and internists to develop training standards in
gone may iterations of development, now including a endoscopy. The standards published in 1976 were quite
wide array of scope/working channel sizes, imaging broad and represented the minimum expected standards to
modalities, and flexion/rotation/degrees of freedom. perform endoscopy [12].

CHEST, 70:1 July 1976
Figure 2.2 Zavala lung model. An early lung model developed
to train physicians in bronchoscopy.
During this time, Dr Zavala developed the first teaching
model for bronchoscopy (Figure 2.2). This model utilized an
existing adult intubation model for the upper airway, with
the Zavala airway substituted distal to the model’s subglottis.
Use of the model allowed for trainees to be introduced to
bronchoscopy while avoiding novice–patient interaction
[13]. An editorial from 1978 questioned the state of training
in bronchoscopy, highlighting the need for observers to rec-
ognize specific pathology. In addition, the first minimum
number of cases was proposed as 50–100 bronchoscopies to
achieve basic competency [14]. In 1980, Dull et al. published
data suggesting no significant difference in bronchoscopic
diagnostic accuracy when comparing instructing physicians
whose experience ranged from 100 to 4000 bronchoscopies.
The authors from this study suggested that performance of
100 bronchoscopies was sufficient to become proficient in
the procedural technique [15].
In 1982, the ACCP again attempted to codify competency
and training standards, this time specifically for fiberoptic
bronchoscopy [16]. These guidelines proposed a minimum
of 50 diagnostic bronchoscopies performed under supervi-
sion and were broken into cognitive and clinical training
objectives. Despite the expertise of the authors, no data
were presented as a basis for their guidance. The 1982
ACCP guidelines were followed in 1987 by the American
Thoracic Society’s (ATS) own guidelines which were
geared toward indications and applications for fiberoptic
bronchoscopy as opposed to competency [17]. Over the
­following two decades, much of fiberoptic bronchoscopy
training was centered on bedside/intraprocedural teach-
ing, one-day courses and the “see one, do one, teach one”
ethos. While effective enough to produce many physicians
skilled in performing bronchoscopy, few data were pub-
lished and basic procedural standards for competency
remained absent.
The Flexible Bronchoscope and Flexible Bronchoscopy Training 23
A number of factors instigated a rising tide of interest in
bronchoscopy training that began in the 1990s. One was
the American Board of Internal Medicine’s requirement
for demonstrated procedural competency in specific proce-
dures for certification in pulmonary critical care and the
acknowledgment that neither the ACCP nor ATS had
delivered data-driven “comprehensive guidelines for grant-
ing hospital privileges to perform the major procedures
associated with the subspecialty of pulmonary and critical
care” [18]. Two other factors were the introduction of high-
fidelity bronchoscopy simulators for resident and fellow
training and the growth of interventional pulmonology
(IP) as a subspecialty.
2.3 ­Bronchoscopy Simulation
In 2000, Haponik et al. published a survey of pulmonary
fellows’ perspectives on their own training in bronchos-
copy. This survey revealed that approaches to bronchos-
copy instruction were primarily in the form of expert
individualized instruction, lecture and case discussion
while use of lung models and review of instructional
videos occurred infrequently. In addition, the authors
noted that nearly a third of participants were unfamiliar
with the technique of bronchoscopic intubation and that
therapeutic bronchoscopic procedures were infrequently
performed. Also noted were high levels of enthusiasm
when using a prototype bronchoscopy simulator. No
measures of skill or procedural quality were undertaken
in this study [19]. Following this, a series of studies vali-
dating and then evaluating high-fidelity bronchoscopy
simulation were published. These data confirmed that
when comparing skill levels between “experts,” “inter-
mediates,” and “novices,” there were significant differ-
ences in procedure time, subjective quality assessment
score, and a quantitative bronchoscopy quality score
[20]. Also noted were significant improvements in
­dexterity and accuracy as demonstrated by fewer missed
airway segments and bronchial wall impacts [21].
Understanding the need for simulated bronchoscopy, di
Domenico et al. presented a recipe to build one’s own
low-fidelity simulation model as an alternative for those
institutions unable to afford high-fidelity virtual bron-
choscopy simulators [22].
These studies were quickly followed by attempts to
marry written/didactic teaching and task-based simula-
tion. The data produced from these publications concluded
that simulation-based practice aided in improvement of
technical bronchoscopy skills and develop of competency-
based bronchoscopy curricula were possible utilizing these
teaching methods [23,24].
24 Flexible Bronchoscopy
Wahidi et al. followed this line of research when they
published a prospective study of the acquisition of bron-
choscopy skills and cognitive knowledge from two cohorts
of pulmonary fellows. The first cohort received bronchos-
copy training per their institutional standards whereas the
second underwent training in a bronchoscopy simulator
and evaluated an online bronchoscopy curriculum. The
two cohorts were asked to complete a series of tasks and
were rated using a validated bronchoscopy skills assess-
ment tool. The results of the study showed a steep learning
curve in the first 30 bronchoscopies for all learners and a
smaller but continuous improvement between 30 and 100
procedures. Skill acquisition did not peak at the 50 bron-
choscopy mark and the educational cohort were found to
have significantly better skills at bronchoscopy milestones
except the 75th procedure [25].
In 2013, a metaanalysis of simulation-based bronchos-
copy training reported significant improvements in
bronchoscopy skills/behaviors and procedural time
associated with simulation training when compared
with no instruction. When comparing standard clinical
instruction with simulation-based training, a nonsignifi-
cant improvement in skills, process, and outcomes was
noted [26]. These studies in simulation-based bronchos-
copy training would ­suggest that its use in training is at
the very least an effective introduction of bronchoscopy
to novices.
2.4 ­Interventional Pulmonology
and Bronchoscopy Training
While in existence for some time, interventional pulmonol-
ogy was truly introduced to the medical and pulmonary
world as an individual subspecialty with an overview/
review of the field published in the New England Journal of
Medicine in 2001 [27]. In this review, Seijo and Sterman
detailed many of the procedural techniques employed by
IP practitioners. This increased awareness and growth of IP
fellowship programs has pushed the field ever closer to
maturity. Along with the growth of IP and practitioners
specifically trained in the performance of advanced diag-
nostic and therapeutic bronchoscopy came an acknowl-
edgment of the need for measures of competency and
standardization of training.
In 2002 and 2003, the European Respiratory Society
(ERS)/ATS and ACCP both published statements on the
practice of IP [28,29]. Both these statement/guidelines
were well thought out attempts to codify the technical
­performance of bronchoscopic procedure as well as to give
some guidance regarding minimum numbers of proce-
dures to achieve and maintain competency. Despite their
best efforts, the authors were forced to rely on scant
­experimental/comparative data on which to make their
recommendations. The ACCP published an expert panel
report in which a PICO question format was used together
with systematic literature searches in an effort to best
understand the state of bronchoscopy training variability
and to give guidance to create procedural training stand-
ards. The panel found a high degree of variability in train-
ing methods although the quantity of data available
remained low (ranges 3–11 studies evaluated per PICO
question). In this publication, a summary table of ERS/ATS
and ACCP guidelines for procedural volume was presented,
but these guidelines primarily represented expert opinion.
Following these guidelines, there were continued incre-
mental gains made in regard to the validation of simulators
and approaches to conventional bronchoscopy training
[23,24,30–34]. As these gains were occurring, however, the
field of bronchoscopy continued to advance with the intro-
duction of EBUS, navigation bronchoscopy, and the rein-
troduction of rigid bronchoscopy. These new technologies
represented great advances in minimally invasive diagno-
sis and staging of patients with lung cancer as well as those
with benign lung disease. With these advances also came
new challenges regarding measures of new procedural
competency, training and a shift in practice pattern. In
2012, Davoudi et al. published a manuscript aimed at eval-
uating an endobronchial ultrasound skills and tasks assess-
ment tool (EBUS-STAT). The EBUS-STAT was used to
evaluate a range of skills and tasks in 24 operators at three
levels of skill – beginner, intermediate and experienced – at
three institutions. They reported high levels of intertester
reliability and an ability to classify EBUS-transbronchial
needle aspiration (TBNA) operators from novice to expert
[35]. In 2013, Feller-Kopman et al. evaluated the effect of
an EBUS-TBNA program on the training of conventional
TBNA (cTBNA) among fellows at a large academic medical
center. The authors reported significant increases in total
cases performed and diagnostic yield when comparing
EBUS to cTBNA. Also noted was a significant decline in
the number of cTBNA procedures as well as diagnostic
yield and accuracy when compared to EBUS [36].
These studies were followed in 2016 when Mahmood
et al. developed a rigid bronchoscopy tool for assessment of
skills and competence (RIGID-TASC). The RIGID-TASC
was to serve as an objective, competency-oriented assess-
ment tool of basic rigid bronchoscopy skills including rigid
intubation and central airway navigation. The authors
evaluated 30 operators at skill levels of novice, intermedi-
ate, and expert at two academic medical centers. They
reported significant differences in RIGID-TASC scoring
across skill levels as well as high levels of intertester relia-
bility [37].

Bronchoscopy skill evaluation tools such as BSTAT,
EBUS-STAT, and RIGID-TASC are the most recent
attempts to quantify and qualify users of basic, advanced,
and interventional bronchoscopy techniques. While not
entirely comprehensive in their approach, they add to a
growing foundation of data aimed at standardizing and
improving the practice of bronchoscopy. A peripheral nav-
igation bronchoscopy assessment tool remains lacking
within the skills evaluation paradigm, with only simula-
tion model data currently available [38,39]. Additional
data generation is needed regarding training and acquisi-
tion of advanced bronchoscopy skills as well as their
maintenance as these modalities become increasingly
ubiquitous in practice. In a recent publication evaluating
the appropriateness of lung cancer staging using EBUS-
TBNA, a significant difference in use of the appropriate
staging paradigm was noted between dedicated high-­
volume users and lower volume practices [40]. These data
suggest that it is not only necessary to adequately learn a
skill but that an as yet defined volume of procedures over
a specific time frame is required not only to perform the
R
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performance paradigm. These complex issues are guaran-
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further research as the technology at our disposal contin-
ues its rapid advance.
2.5 ­Conclusion
We currently stand at a crossroads on the shoulders of a
giant, Dr Shigeto Ikeda. Without his foresight and drive to
develop the flexible fiber videobronchoscope, our ability to
evaluate the airways and disease of the lung might still be
severely limited. While Dr Ikeda certainly never imaged
the development of peripheral bronchoscopy, EBUS or the
evolution of modern-day rigid bronchoscopy, his core val-
ues of patient-centered application of technology, educa-
tion, and instruction continue to drive our practice today.
As we advance further and further, we must not forget to
teach ourselves and our trainees how and when to apply
the amazing technologies of today and tomorrow.
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Applied Anatomy of the Airways
Mani S. Kavuru1, Atul C. Mehta2, and J. Francis Turner, Jr. 3,4
1
Division of Pulmonary and Critical Care Medicine, Jefferson Center for Critical Care, Thomas Jefferson University and Hospital, Philadelphia, PA, USA
2
Lerner College of Medicine, Buoncore Family Endowed Chair in Lung Transplantation, Department of Pulmonary Medicine, Respiratory Institute, Cleveland Clinic,
Cleveland, OH, USA
3
Division of Pulmonary and Critical Care Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA
4
National Supercomputing Institute, University of Nevada, Las Vegas, NV, USA
3.1 ­The Pharynx and Larynx
Flexible bronchoscopy is usually performed via either the
oral or nasal route. Familiarity with the normal anatomy of
this region is important to gain access to the trachea as well as
to recognize local pathology. Certainly, bronchoscopy per-
formed for the evaluation of hemoptysis or wheezing should
include a careful evaluation of the upper airway. The nose
extends from the external nares through the nasal cavity and
the nasal pharynx. Each nasal cavity is bounded medially by
the nasal septum, laterally by the three bony projections
called turbinates or conchae, and inferiorly by the hard pal-
ate that separates the nasal cavity from the mouth. The para-
nasal sinuses open into an area below each turbinate called a
meatus. The blood supply to the nasal mucosa is via branches
of the maxillary artery and the facial artery that anastomose
to form the Kisselbach’s plexus at the anterior medial wall of
the nose, which is a common site of nasal bleeding [1].
The pharynx is 12–15 cm long; it communicates anteri-
orly with the nasal cavity (nasopharynx) and the oral cavity
(oropharynx) and extends to the cricoid cartilage inferiorly
to encompass the hypopharynx or larynx [1]. The pharyn-
geal muscles, including the cricopharyngeous muscle, act
as a sphincter to the proximal esophagus and help to pre-
vent the reflux of esophageal contents. The adenoids or
nasopharyngeal tonsils lie on the posterior wall of the
nasopharynx. The oropharynx is bounded laterally by the
tonsillar pillars, superiorly by the soft palate, anteriorly
and inferiorly by the tongue, and posteriorly by the C2 and
C3 vertebrae. The oropharyngeal cavity is not rigid and is
subject to collapse. The hypopharynx lies between the epi-
glottis and the inferior border of the cricoid cartilage.
Flexible Bronchoscopy, Fourth Edition. Edited by Ko-Pen Wang, Atul C. Mehta, and J. Francis Turner, Jr.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Companion website: www.wiley.com/go/wang4e
27
The larynx, which is 5–7 cm in length and lies at levels
C4, C5, and C6, is a complex organ composed of cartilages,
ligaments, and muscles [1]. An endoscopic view of the lar-
ynx demonstrates the epiglottis anteriorly and superiorly,
aryepiglottic folds bilaterally, with the pyriform sinuses
alongside. The glottis is bounded anteriorly and laterally by
the vestibular folds (false cords) and vocal folds (true cords)
and posteriorly by the arytenoid cartilage [2]. During inspi-
ration, the vocal cords are abducted away from the midline
and the rima glottidis has a triangular appearance. On
expiration, the vocal cords are adducted medially with a
very small opening between them. During maximal abduc-
tion, the distance between the vocal processes is 19 mm in
men and 12 mm in women. In adults, unlike children, the
glottic chink is the narrowest part of the larynx [2].
3.2 ­The Tracheobronchial Tree
The normal adult trachea begins at the lower margin of the
cricoid cartilage and extends 10–14 cm to the bifurcation
into the left and right mainstem bronchi at the level of T5.
One‐third of the trachea is “extrathoracic,” above the level
of the suprasternal notch, and two‐thirds is “intrathoracic”
or below the notch. The average tracheal diameter is 2.5 cm
and is supported anteriorly by 18–24 incomplete C‐shaped
cartilaginous elements and posteriorly by the membranous
trachealis muscle. In the normal adult, the diameter of the
entire trachea is well maintained throughout the respira-
tory cycle by the rigid support of the tracheal elements. In
patients with obstructive airways disease or older individu-
als, the tracheal lumen may be reduced dynamically with
28 Flexible Bronchoscopy
coughing or during expiration because of collapse of the
posterior membranous wall anteriorly [3].
Normally, the aortic arch compresses the mid to distal
left lateral wall of the trachea to the right. The adult tra-
cheal width–depth ratio can vary from 0.6 (high‐domed
variant) to 3.0 (lunate variant). The main carina is normally
quite sharp and is mobile during the respiratory cycle [4].
The right mainstem bronchus normally bifurcates at an
angle of 25–30° from the midline, with a luminal diameter
of around 16 mm and an average length of 2 cm before the
bifurcation of the right upper lobe bronchus from the right
mainstem bronchus. The right upper lobe orifice averages
10 mm and usually branches into the apical, posterior, and
anterior segmental bronchi [5]. After the bifurcation of the
right upper lobe bronchus, the right mainstem bronchus
continues as the bronchus intermedius.
The anterior wall of the bronchus intermedius continues
to become the right middle lobe, which divides into the
medial and lateral subsegments. By virtue of its anterior
location, foreign bodies have a propensity to continue from
the trachea and fall into the right middle lobe. The right
lower lobe bronchus represents the posterior continuation
of the bronchus intermedius, further dividing into five sub-
segments with frequent variation [6]. The superior or api-
cal subsegment usually arises posteriorly opposite to the
origin of the middle lobe bronchus. Next, the medial basal
subsegment arises on the medial wall and may subdivide
further. The right lower lobe subsequently divides into the
anterior, lateral, and posterior basal subsegments. These
three subsegments are usually stacked one on top of the
other proceeding from anterior to posterior configuration
(A–L–P).
The left main stem bifurcates from the trachea at a sharp
45° angle from the midline. It is narrower and much longer
than its counterpart, with an average length of 5 cm. The dis-
tal left mainstem bronchus primarily divides into the left
upper and left lower lobe. The upper divides into the lingular
division (composed of the superior and inferior lingular sub-
segments) and the upper lobe division (composed of the api-
cal posterior and anterior subsegments). The lower lobe
initially gives rise to the superior or apical subsegment,
which is posteriorly located. The left lower lobe subsequently
divides into the anterior medial, lateral, and posterior basal
subsegments. There is again considerable variability in the
basilar subsegments of the left lower lobe [6,7].
3.3 ­The Relationship of Airways
to Lymph Nodes and Vessels
As important as a thorough understanding of the normal
endobronchial anatomy and the frequent congenital varia-
tions is thorough familiarity with normal structures that
reside outside the airway in intimate juxtaposition to the
airway [8]. This knowledge is mandatory with the increas-
ing use of endobronchial diagnostic and therapeutic
modalities, including transbronchial needle aspiration
(TBNA), laser therapy, and endobronchial radiation ther-
apy. This anatomic knowledge will help facilitate access to
lymph nodes or extraluminal mass lesions that may be
important in either diagnosis or staging [9,10] and
will hopefully avoid inadvertent access of vascular struc-
tures that are intimately associated with the airways in sev-
eral areas.
The posterior aspect of the trachea is closely associ-
ated with the esophagus. The aortic arch lies anterior
and to the left of the distal one‐third of the trachea and
makes an easily recognizable pulsatile imprint on the
anterolateral tracheal wall; this area should be avoided
for obvious reasons [8]. The superior vena cava and the
azygos vein lie anteriorly and to the right of the distal
third of the trachea. The aortic arch and the innominate
artery lie directly anterior to the trachea at the level of
the main carina. The right pulmonary artery lies imme-
diately anterior to the right mainstem bronchus and the
origin of the right upper lobe bronchus. There is signifi-
cant variability in the relationship of vascular struc-
tures to the right middle lobe and lower lobe bronchi.
The aortic arch and left pulmonary artery are in close
association to the left mainstem bronchus and left
upper lobe bronchus.
Lymph nodes lie in close association to the airway. The
paratracheal lymph nodes lie on either side of the length
of the trachea in a posterolateral distribution. The right
paratracheal lymphatic drainage is most easily accessed
at one or two tracheal rings above the main carina
before the bifurcation on the right posterolateral aspect
(Figure 3.1). The subcarinal mediastinal lymph nodes
normally lie immediately inferior to the main carina. This
chain can be most easily sampled not by direct aspiration
of the main carina itself, but by entry with a transbron-
chial needle 3–5 mm below on either side of the main
carina with a lateral to inferomedial entry (Figure 3.2).
This minimizes having to pass through the cartilaginous
element itself. Hilar lymph nodes may be sampled at
either the secondary carina, where the right upper lobe
bifurcates from the bronchus intermedius, or at the level
of the secondary carina, where the left upper lobe bifur-
cates from the left mainstem bronchus (Figure 3.3). The
right pulmonary artery is in close association with the
anterior wall of the right upper lobe bronchus so TBNA
and other procedures are not recommended at this site
(Figures 3.4 and 3.5).
The left paratracheal lymph nodes are located at the origin
of the left mainstem bronchus from the main trachea
(Figure 3.6). This chain is particularly difficult to sample;
 Applied Anatomy and Physiology of the Airways 29

(a) (b)

Pulmonary
veins
Left Right

Pulmonary
Left trunk
Pulmonary
trunk pulmonary
artery
Right pulmonary
artery
Aorta
Superior Right main
vena cava stem bronchus

Left main Superior

Aorta vena cava
stem
bronchus Right paratracheal
lymph node
Right
paratracheal
lymph node
Azygos Trachea
vein
11 12 1
10 2
Left main Main Right main 9 3
stem bronchus carina stem bronchus
8 4
7 6 5

Figure 3.1 Representation of normal anatomic relationships at the level of the distal trachea. (a) The endoscopic view of the distal
trachea, with adjacent vessels and lymph nodes superimposed. The right paratracheal lymph node is between the 1 and 2 o’clock
position, whereas the azygos vein is located at the 3 o’clock position. (b) An endoscopic clockface view. The arrow between 1 and 2
o’clock indicates the proper site for TBNA of the right paratracheal lymph node. The arrow at 3 o’clock indicates the unsafe location
for aspiration (azygos vein).

(a) (b)
Main
carina
Pulmonary
veins
Left Right

Pulmonary
trunk
Left
pulmonary
artery Right pulmonary
Left main Right main artery
stem bronchus stem bronchus
Right main
stem bronchus
Aorta Superior
Left main vena cava
stem bronchus

Subcarinal Subcarinal
lymph nodes lymph node
Trachea

11 12 1
10 2

9 3
8 4
7 6 5

Figure 3.2 Representation of the normal anatomic relationships at the level of the main carina. (a) The endoscopic view of the main
carina, with surrounding lymph nodes superimposed. (b) An endoscopic clockface view at the right mainstem bronchus orifice. The
arrows at the 8 and 11 o’clock positions indicate the proper site for TBNA of subcarinal lymph nodes.

however, aspiration can be performed by using a transbron- f­ acilitating entry of the needle laterally. Figure 3.7 illustrates
chial needle anchored to the lateral tracheal wall of the distal the association of left upper lobe bronchus and the left pulmo-
trachea at the level of the carina with a subsequent down- nary artery. Figure 3.8 illustrates the location of left hilar
ward or inferior movement of the entire bronchoscope, hence lymph nodes.
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